Diastereoselective and Enantioselective Synthesis of Homopropargyl and Allenylcarbinols from Nonracemic Propargyl Mesylates via the Derived Allenyl and Propargyl Trichlorosilanes
Diastereoselective and Enantioselective Synthesis of Homopropargyl and Allenylcarbinols from Nonracemic Propargyl Mesylates via the Derived Allenyl and Propargyl Trichlorosilanes
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DOI：
10.1021/jo971853l
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发表时间：
1997-12
影响因子：
3.6
通讯作者：
J. Marshall;Nicholas D. Adams
中科院分区：
文献类型：
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作者：
J. Marshall;Nicholas D. Adams
在涉及生物活性聚丙酸酯和聚醚天然产物的全合成项目中，我们一直在探索手性丙二烯基和炔丙基有机金属试剂与醛的SE2'加成反应，分别生成均丙炔醇和丙二烯基甲醇。这些研究的初步工作表明，通过对映体富集的丙炔甲磺酸酯 I 的 SN2' 置换获得的手性丙二烯基锡烷 II，在适当的反应条件下可提供高对映体纯度的均炔丙醇 III 或丙二烯基甲醇 V（式 1）。 1, 2 前者代表聚丙酸酯合成的可能中间体，3 和后者充当聚醚四氢呋喃亚单元的前体。 1Kobayashi 及其同事最近关于将烯丙基和炔丙基三氯硅烷添加到醛中的研究结果促使我们考虑一种替代的、可能更直接的方法来生成与 III 和 V 相关的加合物。 4, 5 该方法的适当扩展将涉及使用取代的手性丙二烯基或炔丙基卤化物 1 或 3 作为炔丙基或丙二烯基三氯硅烷中间体的前体，这些中间体将添加到醛中以提供高炔丙基或丙二烯基加合物 2 或 4（表 1）。为了测试甲硅烷基化方案的可行性以及随后添加的区域选择性和非对映选择性，我们对外消旋联烯基卤化物 1 和炔丙基卤化物 3 与苯甲醛进行了初步实验。这些实验的结果总结于表 1 中。
In connection with projects involving the total synthesis of bioactive polypropionate and polyether natural products, we have been exploring SE2′ additions of chiral allenyl and propargyl organometallic reagents to aldehydes leading to homopropargylic and allenylcarbinols, respectively. Initial efforts in these investigations showed that chiral allenylstannanes II, obtained by SN2′ displacements of enantioenriched propargylic mesylates I, afford either the homopropargylic alcohols III or allenylcarbinols V of high enantiomeric purity under appropriate reaction conditions (eq 1). 1, 2 The former represent possible intermediates for polypropionate synthesis, 3 and the latter serve as precursors of tetrahydrofuran subunits of polyethers. 1Recent findings by Kobayashi and co-workers on additions of allylic and propargylic trichlorosilanes to aldehydes led us to consider an alternative, and possibly more direct, approach to adducts related to III and V. 4, 5 The appropriate extension of this methodology would involve the use of substituted chiral allenyl or propargyl halides 1 or 3 as precursors to propargyl or allenyl trichlorosilane intermediates that would add to aldehydes to afford the homopropargyl or allenyl adducts 2 or 4 (Table 1). To test the feasibility of the silylation protocol and the regio-and diastereoselectivity of the ensuing additions, we conducted preliminary experiments on the racemic allenyl and propargylic halides 1 and 3 with benzaldehyde. The results of these experiments are summarized in Table 1.